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J. Hadžiabdić, A. Elezovic, S. Hadžović, M. Vehabović

When the fast absorption of diazepam is needed in order to suppress febrile convulsions and epileptic seizures, the most suitable is intravenous application diazepam. To avoid inappropriate self administration of such diazepam dosage form, orodispersible tablets of diazepam would be the dosage form of choice. Poor solubility of diazepam in water is directly related to its dissolution rate after release from a solid dosage form. Inadequate dissolution rate of diazepam can be the limiting factor for its absorption rate. Inclusion complexation of diazepam with 2-hydroxypropyl-β-cyclodextrin was carried out to increase the solubility of diazepam at pH 6.8. Determination of the intrinsic dissolution rate of diazepam as well as complexated diazepam was carried out to predict the absorption rate of diazepam at given pH value. The solubility of micronized diazepam (particle size 5.4 µm) at pH 6.8, was 0.043 mg mL-1, while the solubility of non-micronized diazepam (particle size 414.8 µm) at the same pH was 0.036 mg mL-1. Inclusion complexation of diazepam with 2-hydroxypropyl-β-cyclodextrin resulted in increased solubility of diazepam. One mole of 2-hydroxypropyl-β-cyclodextrin increased the solubility of micronized diazepam 6.82 fold, while two moles of 2-hydroxypropyl-β-cyclodextrin increased the solubility of diazepam 12.55 fold. Given that the values of intrinsic dissolution rates (IDR) of micronized diazepam, non-micronized diazepam and inclusion complex D: 2-HP-β-CD 1:1 were less than 0.1 mg min-1 cm-2, the absorption of diazepam dissolution would be the rate limiting step to absorption, while the inclusion complex D: 2-HP-β-CD 1:2 where an IDR value was greater than 0.1 mg min-1 cm-2 at pH 6.8, suggested that its dissolution might be the rate-limiting step to absorption. Hydroxypropyl-β-cyclodextrin increased the solubility of diazepam at pH 6.8, thus increasing the dissolution rate and causing faster absorption of diazepam at pH 6.8.

A. Elezovic, A. Elezović, S. Hadžović

Nail lacquers represent new drug form specifically designed to treat infected nail plate. They are complex organic solutions with specific assaying problems due to the high content of the polymer and plasticizer. Furthermore, there is a lack of assaying methods of active substances from this type of formulations in scientific literature. We developed derivative UV-spectrophotometric method for determination of fluconazole content in antifungal nail lacquer formulations. The method was validated for specificity, linearity, precision (repeatability), intermediate precision and accuracy (recovery). The method is specific, linear in the range of 99.53 - 497.65 μg/ml, precise and showed good recovery (98.79% - 101.77% from all six developed formulations). Besides, it is inexpensive, simple and nontoxic, i.e. ecologically acceptable. This method can be used for assaying fluconazole from this type of formulations.

A. Elezović, S. Hadžović, Š. Hadžidedić, S. Kostic

Onychomycoses, fungal nail infections, are responsible for 50% of all nail disorders affecting up to 18% of general population in some countries [1]. [...]

E. Vranić, O. Planinšek, Andrijana Tivadar, S. Hadžović, S. Srčič

For the majority of the pharmaceutical dosage forms, the substances that are used maintain solid state under the standard storage conditions, i.e. powders. The interactions of pharmaceutical powders (active ingredient(s) and excipients) with liquids and vapors (particularly aqueous solutions and their vapors) occur almost always during the production process. From the physical point of view, the interactions among individual components may differ from the expected because chemically identical substances obtained from different producers vary very much. These differences influence either the production process and/or the pharmaceutical form properties. In order to overcome these problems it is necessary to establish a control over the physico-chemical properties of the used materials. The aim of this work was to determine physico-chemical properties of three powder clindamycin phosphate samples (labeled as sample S(1), S(2) and S(3)) acquired through different suppliers. All the analysis were made for the purpose of establishing possible differences among the tested samples that showed variable physical stability in the solution: recrystallization of the S(3) sample in the aqueous solution has been established during storage under standard conditions. On the basis of the obtained data it was possible to recognize the differences among the tested clindamycin phosphate samples and to explain the anomalous behavior of one sample. The surface free energy components for the investigated clindamycin phosphate samples were determined using Wu and Good- van Oss method. The investigated clindamycin phosphate samples exhibit certain differences in surface free energy values as well as in surface morphology and thermal behavior. Comparison of alpha + and alpha - values leads to the conclusion that all three clindamycin phosphate samples perform as monopolar, more electron acceptors, i.e. Lewis acids. However, an important difference exists between samples S(1) and S(2) on one and S(3) on the other side. Sample S(3) exhibits stronger acidic behavior, what could be connected with its recrystallization during the storage. The samples S(1), S(2) and S(3) have different melting points e.g. "onset" temperatures. When the melting points move towards 200 (o ) C, the width of the "onset" temperature peak is especially important. In the case of wider peak, the potential for recrystallization seems to be higher. According to the stated, the sample S1 would be the "sample of choice" for the formulation of the stable pharmaceutical dosage form and has not shown any recrystallization tendencies during the storage period.

M. Vehabović, S. Hadžović, Fatima Stambolic, Amina Hadzic, E. Vranjes, E. Haracic

A. Mehmedagić, E. Vranić, S. Hadžović, M. Pokrajac, J. Milić, B. Mehić, H. Zutić, A. Konjicija

Sustained-release theophylline pellets formulation for once-daily evening administration significantly improved patients compliance and adjusted serum levels profile of the drug. The patients conversion from i.v. to p.o. therapy is one of the most critical steps in the treatment of asthma according to its chronopathophysiological character. In our study we have examined safety and efficiency of this conversion in twelve hospitalised asthmatic patients who were given the new sustained-release theophylline pellets formulation for once-daily evening administration. The lung function parameters (FEV1, VC, RV, and Rt) and serum theophylline concentrations were monitored. So, the values obtained for the last day of i.v. therapy and the fifth day of p.o. therapy were compared. We found that 75% of the patients had no change or improved lung function on the conversion. Our results indicate that this conversion from i.v. to p.o. theophylline therapy is safe and could be efficacious. Also, the maximum theophylline serum levels could safely be predicted by measuring only one serum concentration in p.o. therapy with sustained-release theophylline pellets formulation for once-daily evening administration.

In recent years, drug release/dissolution from solid dosage forms has been the subject of intense and profitable scientific developments. Whenever a new solid dosage form is developed or produced, it is necessary to ensure that drug dissolution occurs in an appropriate manner. The pharmaceutical industry and the registration authorities do focus, nowadays, on drug dissolution studies. The quantitative analysis of the values obtained in dissolution/release tests is easier when mathematical formulas that express the dissolution results as a function of some of the dosage forms characteristics are used. This work discusses the analysis of data obtained for dissolution profiles under different media pH conditions using mathematical methods of analysis described by Moore and Flanner. These authors have described difference factor (f1) and similarity factor (f2), which can be used to characterise drug dissolution/release profiles. In this work we have used these formulas for evaluation of dissolution profiles of the conventional tablets in different pH of dissolution medium (range of physiological variations).

Even in 15th and 16th century there were people in Bosnia, preparing medicaments and selling different kinds of medical herbs. At first, they were Jews, later Muslims. They were called "attars"--drugsellers. They were very familiar with herbs of medical purpose. They could recognize herb by its colour and outlook. The goods were sold in specialized shops--attar shop. When analysing Materia Medica from an attar shop--according to the list from the 1911 (dr. Moritz Levy: "Sefards in Bosnia"), we can conclude that assortment of medical herbs and some medicaments was correct. Some Galen forms used in that time, are still in use nowadays. This paper describes all materials encompassed by Materia Medica. They are classified as organic and non-organic materials, and their use in therapy was also emphasized. Materia Medica of attar shops gives us a lot of material for research of non-official medicine and pharmacy from that time.

The differentiation and separation of two scientific disciplines, medicine and pharmacy begins during the 12th century. Each differentiation by itself brings certain improvement and upgrading but at any level, this happens only when proper conditions are met. Therefore, in order for pharmacy to appear as a profession and to promoted to the level of science, certain conditions had to be met, namely the society and cultural forces had matured to the level of differentiation of these two disciplines, which have begun existing as completely independent disciplines in that time. For the history of pharmacy, it is very important to note the fact that we find the first beginnings of professional pharmacy among Arabic population. The first drug stores in the world were established in Arabic world (Baghdad 754). Considering the fact that Arabs had brought a great deal to pharmaceutical science and the fact that their search included some 2.000 substances, the goal of this work was formulated and medicinal herbs used in the treatment listed. The forms used that period are still used in the therapy and some formulations of drugs can be found in pharmacopeas even today. If we add to these reports the fact that most of the literature appearing in the field was also of Arabic origin and that many editions and translations of the pharmaceutical works from Arabic to Latin had been published ever since, the obvious contribution of Arabic science in the development of pharmacy becomes even more obvious.

The gallenic drugs manufacturing often represented necessary substitution in the commercial products deficiency, for a short time-period, whereas in a war conditions could supplement and/or substitute some commercial products. As information about commercial products we used the Pharmacotherapeutical handbook and the Basis pharmaco-informing data register, whereas the manufacturing of the gallenic drugs are established by the general instructions of the Yugoslav Pharmacopoeia in this paper in which the possibilities of the commercial products substitution were shown. The aim of the paper was to reaffirm existing materia medica performances, supplement the existing offer of gallenic drugs and alleviate increasing lack of commercial drug products.

The development of pharmacy and dispensaries in Bosnia and Herzegovina started very early and it could be divided into several periods from which we select the period of Turkish and Austro-Hungarian rules as they had organized activities. In remote times, beginnings of treatment of diseases belong to herbalists who in our parts even then were a significant guild. That guild saw an intensive development in the times of Turkish rule. In Sarajevo, the sale of medicines in shops was established as early as that period. They resembled today's drugstores and had supervision of the condition and use of medicines which was done strictly. The Austro-Hungarian period in Bosnia and Herzegovina meant a great change in the development of pharmacy and health care generally and since then pharmacy and dispensaries in Bosnia and Herzegovina have been organized according to European standards, while the care of making dispensing and trading in medicines was taken over by trained pharmacists.

J. Milić-Aškrabić, S. Hadžović, Z. Samardzic

Comparison of extrapyramidal side effects of two fluphenazine hydrochloride injections. Lyogen and Moditen was carried out by the in vivo experiments in mice. The incidence, intensity and duration of the catalepsy in mice after i. m. application of 10 mg/kg fluphenazine hydrochloride in two forms of sterile water solution have been observed. Catalepsy of significant intensity occurred after a short period of 15 minutes regarding the both formulations and maximal values were observed 30 and 60 minutes after application of Lyogen, and Moditen respectively. Significant values of cataleptic intensity with respect to control group (the water for injection-treated group) were registered during 28 hours after the application of both formulations. This study of cataleptic effects could not confirm significant differences between these two formulations, between the rate of occurrence and duration of effects. On the other hand, the difference between intensities were observed and were more prominent in the period between 6-24 hours. An the most cases they were not significant (p greater than 0.05).

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